Evidence for a Temperature Dependent Reversal of the Enantioselectivity in Complexation
Gas Chromatography on Chiral Phases.

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N-TFA-tert-butyl amides of a-amino acids can intercalate
between a diamide solvent in either a parallel (C) or an
antiparallel (D) fashion (Scheme 1). The resulting hydrogen bonded structures and the orientation of the asymmetric centers towards each other are not the same. For
each of these two modes of intercalation there should be a
corresponding In a vs. 1/T plot analogous, respectively, to
the curves with a > I and a < I of Figure 2. Superimposition of such individual contributions to the total resolution, if of appropriate magnitude, could lead to an overall
curve, as found experimentally, i.e., a linear branch, inversion and an inflexion point.
+I
C
[2] M. Lederer (Proc. h l . Congr. Surf. Acl. 2nd 1957, p. 578) used the
Gibbs-Helmholtz relationship to correlate the variation of Rt values
with temperature.
[3] M. R. Hoare, Y. H. Purnell, J. H. Purnell, Trans. Faraday Soc. 52 (1956)
222.
141 B. Koppenhofer, E. Bayer, Chromarographia 19 (1984) 123.
IS] V. Schurig, R. Link, unpublished.
I61 R. Charles, E. Gil-Av, unpublished results.
[7] S.-C. Chang, R. Charles, E. Gil-Av, J. Chromarogr. 202 (1980) 247.
[8] Preliminary communication; see K. Watabe, R. Charles, E. Gil-Av, Inr.
Symp. Adu. Chromafoyr.23rd 1986 (Chiba, Japan), Abstracts p. 83.
191 S.-C. Chang (University of Gainsville, FI.), personal communication.
[lo] B. Koppenhofer, personal communication.
[I 11 We wish to thank Prof. V. Schurig for communicating his relevant observations in complexation gas chromatography prior to publication: see V.
Schurig, J. Ossig, R. Link, Angew. Chem. 101 (1989) 197; Angew. Chem.
Int. Ed. Engl. 28 (1989) 194.
[12] Dilution of diamide selectors by apolar solvents causes an increase of
the resolution coefficients of the N-TFA a-amino acid esters 1131. This
has been ascribed to dissociation of the hydrogen bonded network of
the selector and to the higher stereoselectivity of the non-associated
form. A similar change could occur on raising the temperature, leading
to an upward curvature of the Gibbs-Helmholtz piot and implying that
M H ” and/or M S o depend on the temperature.
I131 T. Hobo, S. Suzuki, K. Watabe, E. Gil-Av, Anal. Cbem. 57 (1985) 364.
1141 B. Feibush, A. Balan, B. Altman, E. Gil-Av, J. Cbem. Soc. Perkin Trans.
2 1979, 1230.
[lS] H. Pracejus, A. Tille, Cbem. Ber. 96 (1963) 854.
[I61 I. Ugi, Chimia 40 (1986) 340.
Evidence for a Temperature Dependent Reversal of
the Enantioselectivity in Complexation
Gas Chromatography on Chiral Phases**
D
By Volker Schurig,* Joachim Ossig, and Rainer Link
Scheme I.’ Parallel (C)and antiparallel (D) intercalation of an N-TFA-La-amino acid fert-butylamide in a diamide selector, with hydrogen bonding
of type ‘‘CS-C7”(C)and “C7-C7” + “Cs-Cs” (D).
The proposed explanation is supported by the behavior
of the N-TFA-tert-butyl amide of proline. This diamide selectand cannot intercalate between the phase molecules, as
shown in Scheme 1, and indeed, behaves quite differently
from the other diamide selectands (see Fig. 1). It should be
emphasized that such a double mechanism of resolution
(Scheme 1) is not a condition for the observation of inversion, but it might shift the T,,, point into a favorable
range.
In conclusion, the sense of the stereoselectivity of a chiral selector-selectand system is not to be considered a constant property, but is temperature dependent. This is of
particular importance for the determination of configuration from chromatographic data. In many cases, however,
inversion of the order of elution cannot be observed,
largely because of too high T,,, points. It is noteworthy
that a temperature dependent inversion of the chirality of
the products of certain stereoselective reactions has been
obserVedi’S.161
and was interpreted analogously in terms of
the Gibbs-Helmholtz relationship involving the thermodynamic parameters of the relevant transition states.[’61
Received: August 12, 1988 [Z 2924 IE]
German version: Angew. Chem. 101 (1989) 194
[I] In this communication a=a,,,, i.e., the ratio of the adjusted retention
volumes of the L- and D enantiomers. For a> I, the D-isomer is eluted
before the L-isomer. for a < I, the opposite applies.
194
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A temperature dependent reversal of the enantioselectivity (i.e., of the sign of AR.,(AGn)) of a defined, nonracemic stationary phase (selector) in the chromatographic
separation of a chiral substrate (selectand) has been predicted on the basis of the temperature term in the GibbsHelmholtz relationship (a)[’]
RTln(KR/KS)= -AR.s(AGO)= -AR,S(AljO)+ TARs(AS0)
(a)
T,,,=AR.S (A@)/AR,, (ASo)
(b)
(where R arbitrarily represents the enantiomer which is
eluted after its S antipode from a chiral column). When
AR,S(AGn)= 0 ( K R= K s , no enantiomer separation), the
isoenantioselective temperature T,,, [Eq. (b)] is reached. At
TI,,, peak coalescence (‘of the third kind”’]) occurs; below
it the order of elution is governed by -AR.s(AH“> and
above it by AR,,(ASn)). At the coalescence temperature
Tiso(no enantiomer separation) the sign of enantioselectivity will change.I3I
The first gas chromatographic evidence for a temperature dependent reversal of the enantioselectivity of a chiral
stationary phase was obtained by Watabe, Charles and
Gil-Av in a hydrogen-bonding selectand-selector system.[41
Here we report a further example which was observed by
enantioselective coordination in complexation gas chromatography and is characterized by a low value of qso.
In the gas chromatographic separation of the enantiomers
of (9-2-ethyl- 1,6-dioxaspiro[4.4]nonane l b on nickel(I1)bis[3-(heptafluorobutanoyl)-( 1s)1 0-methylenecamphorate]
[‘I Prof. Dr. V. Schurig, Dipl.-Chem. J. Ossig, Dr. R. Link
[**I
Institut fur Organische Chemie der Universitat
Auf der Morgenstelle 18, D-7400 Tubingen (FRG)
This work was supported by the Deutsche Forschungsgemeinschaft and
the Fonds der Chemischen Industrie. We wish to thank Prof. E. Gil-Au,
Rehovoth, Israel, for communicating his results prior to publication.
0570-0833/89/0202-0194 $ 02.50/0
Angew. Chem.
Inr. Ed. Enyl. 28 (1989) No. 2
A
l a = A + B
Za,
l b = C + D
Zb, R = CH=CH,
R
= CH3
+
2blS1 the coordination interaction (K,,,, = ( K c K D ) / 2 )
steadily decreases between 30°C and 1500C. No separation of the enantiomers C and D is observed between
70°C and 90°C. At 60°C D is eluted after C whereas at
140°C C is eluted after D (Fig. 1). Most important is the
observation that enantiomer discrimination increases with
increasing temperature above the coalescence region (Fig.
2), although the total coordination interaction decreases,
as expected. Thus, the requirement of the Gibbs-Helmholtz equation of an increase of AD,C(AGO) above T,,, is
fulfilled. Unfortunately, because of the decrease of the selectand-selector coordination at higher temperatures and
the configurational lability of the chiral spirocenter of 1,
which causes characteristic interconversion profiles1z,61
(cf.
Fig. 2), investigations could only be carried out up to
150°C.
The determination of the Gibbs-Helmholtz parameters
of the enantioselective association between l b and 2b
from relative retention
revealed a linear relationship between R . In ( K D / K c ) and 1/T (measured at five de-
'L
80
+
.I
i,
t lminl
20
40
60
80
t[minl-
120
100
140
,
160
Fig. 2. Peak coalescence ('of the third kind) for the enantiomers C and D of
l b (racemic) in complexation gas chromatography on 2b (0.1 M in OV-101)
at 80°C and increase of enantiomer discrimination with increasing temperature. Column: 34.2 m x 0.25 mm glass capillary, carrier gas: 1.0 bar N2.
C1,= n-undecane, C 1 2= n-dodecane.
gree intervals between 50 and 65°C) with -AD.c(AHo)
=0.62 kcal mol-' and AD.,-(AS0)=-1.75 cal mol-'
K-',''] from which T,,,=354 K (80°C) is calculated[91(Fig.
3); this value is in agreement with the experiment (Fig. 2).
Peak coalescence is observed for the enantiomers A and B
of the (z) diastereomer l a at 60°C.
T : 140°C
-
I
0
i
I
/
"/
/'
/
3.00
2.83
lo3/ TIK"1
/
+An.c(A Gal
-
Fig. 3. Extrapolation to determine the isoenantioselective temperature T,,,
for the separation of Ib on 2b. R.ln (KD/Kc)
(T["C]): 0.165 (50); 0.136 (55);
0.104 (60); 0.0805 (65).
0
tlminl
-
30
Fig. I . Temperature dependent reversal of the enantioselectivity of 2b (ca.
0.15 M in OV-101) in the separation of l b (enriched in the D enantiomer) by
complexation gas chromatography. Column: 25x11x 0.25mm fused silica capillary, 0.2 p stationary phase, carrier gas: N2. C, = n-hexane (solvent),
C , , = n-undecane, C I 2= n-dodecane.
Angew. Chem. Inr. Ed. Engl. 28 (1989) No. 2
The findings could well be of considerable importance
for the understanding of mechanistic aspects of enantioselectivity in chromatography, in particular, and of enantiomer recognition in chiral environments, in general. The
influence of temperature on the discrimination of enantiomers will now have to be considered in rationalizing
chiral recognition. In complexation gas chromatography,
exceptions[*l to the rules correlating the absolute configurations of structurally closely related selectands with their
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195
order of elution from chiral selectors["' as well as unsatisfactory enantiomer separation for particular selectands'"]
may well be due to the temperature dependence of the enantioselectivity, particularly for temperatures close to Ti,,.
It is intriguing to realize that above T,,,, preferential recognition of one enantiomer is not caused by stronger binding
to a non-racemic matrix but is due to the higher degree of
disorder in the resulting chemical interaction.
be able to exhibit optical activity.['.31 By copolymerizing
the mannitol derivative 1 with different comonomers and
subsequent cleavage of the mannitol template, optically
active copolymers (e.g., poly(4-vinylphenylboronic acidco-styrene)) consisting of asymmetric triads of type 2 were
~btained.[~-~]
Received: August 23, 1988 [Z 2938 IE]
German version: Angew. Chem. I01 (1989) 197
[I] a) B. Koppenhoefer, Dissertation, University of Tiibingen 1980; b) B.
Koppenhoefer, E. Bayer, Chromalographia I9 (1984) 123; c) V. Schurig,
Angew. Chem. 96 (1984) 733; Angew. Chem. Inl. Ed. Engl. 23 (1984)
741.
121 V. Schurig, W. Burkle, J. Am. Chem. SOC.104 (1982) 7573.
[3] In principle, a temperature-dependent reversal of the enantioselectivity
may also arise from structural or configurational changes in the nonracemic stationary phase upon heating or from changes of the individual
contributions of compeling mechanisms of chiral recognition.
[4] K. Watabe, R. Charles, E. Gil-Av: 23rd Znt. Symp. Adu. of Chromatogr.
1986 (Chiba, Japan), Abstracts, p. 83; cf., Angew. Chem. 101 (1989) 194;
Angew. Chem. Int. Ed. Engl. 28 (1989) 192.
[S] V. Schurig, A. Ossig, R. Link, J . High Resolut. Chromatogr. Chromatogr.
Commun. I 1 (1988) 89.
[6] a) V. Schurig in J. D. Morrison (Ed.): Asymmetric Synthesis, Vol. Z , Academic Press, New York 1983, p. 59; b) V. Schurig, J . Chromotogr. 441
(1988) 135.
[7] V. Schurig, R. Link in D. Stevenson, I. D. Wilson (Eds.): Chiral Separations. Plenum, London, in press.
[8] The enantioselective selectand-selector system l b and 26 shows some
unusual features which are not fully understood at present. Although
the temperature-dependent reversal of the elution order of l b on Zb is
fully reproducible, - A o . c ( A G o ) = R T . l n ( K D / K c ) almost doubled at,
e.g., 60°C with increasing time of operation of the column, while K,,,.
remained essentially unchanged. Also, an excessive peak-broadening,
reaching a maximum at T,,, has been observed both for the racemic mixture and the single enantiomers.
[9] Recently, in a careful study of the temperature dependence of the separation of l a and l b on Za (1R)in SE-54 polysiloxane in five degree
intervals between 80 and 120°C, T,, values as high as 200°C have been
extrapolated for these Z / E isomers [7].
[lo] V. Schurig, B. Koppenhofer, W. Biirkle, Angew. Chem. 90 (1978) 993;
Angew. Chem. Znt. Ed. Engl. 12 (1978) 937.
[ I 11 Thus, isopropyloxirane is not resolved on 2a at 60°C (T,=) [2]. Besides,
it also shows a temperature dependent reversal of the elution sequence:
V. Schurig, D. Wistuba, unpublished.
Can Polystyrene be Optically Active?**
By Giinter Wuvf* and Pradeep K . Dhal
Dedicated to Professor Kurt Heyns on the occasion of his
80th birthday
The question, as to whether polymers based on vinyl
monomers can exhibit optical activity arising from a chiral
configuration of the main chain (main chain chirality) has
long been a subject of discussion. The conclusion of this
debate, after consideration of all the commonly encountered and well-known structures of both homo- and copolymers, revealed that they are not expected to exhibit any
such characteristics.[*] Careful symmetry considerations
have shown recently that, particularly in the case of copolymers, several chiral structures are possible which should
[*I Prof. Dr. G. Wulff, Dr. P. K. Dhal
Institut fur Organische Chemie und
Makromolekulare Chemie der Universitat
Universitatsstrasse I , D-4000 Diisseldorf (FRG)
[**I On the Chirality of Polyvinyl Compounds, Part 9. This work was supported by the Minister fur Wissenschaft und Forschung des Landes
Nordrhein-Westfalen and the Fonds der Chemischen Industrie. Part 8:
111.
196
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R
9
R
I
1
0i 4 9
I
R
n
2
3
In this example, the diads having A substituents (4vinylphenyl boronic acid residues incorporated via the
mannitol derivative 1) are decisive for chirality (in this
case, the diad has the (S,S)-configuration).[61The carbon
atoms bearing B substituents d o not represent stereogenic
centers and essentially serve to separate the chiral diads
from one another. Therefore, this spacer can also be composed of a relatively long chain fragment (stereoregular or
atactic) of comonomer units (see 3).1',61 This gives rise to
the question of whether a chain fragment consisting of an
atactic sequence of homopolymer could fulfill the requirements of a spacer for the diads as well. If this were so, it
would be possible to prepare, for the first time, optically
active vinyl homopolymers possessing well-defined main
chain chiral configurations.
In order to address this question, a systematic model
study was carried out for all possible partial chain structures. We analyzed to what extent the asymmetric arrangement at the centers of the diad, which originally had a defined absolute configuration, is retained upon introduction
of intermittent atactic units. The following essential simplifications were introduced:
a) Chain fragments consisting of one, two, o r three monomer units with a statistical distribution of all possible
configurations, were considered to serve as appropriate
bridging groups between the diads in 3.
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Angew. Chem. Znl. Ed. Engl. 28 (1989) No. 2